RNA-based genetic switch using synthetic small molecular ligands that control RNA structure and function
Project/Area Number |
18H02107
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 37030:Chemical biology-related
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Research Institution | Osaka University |
Principal Investigator |
DOHNO Chikara 大阪大学, 産業科学研究所, 准教授 (60420395)
|
Project Period (FY) |
2018-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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Keywords | リボザイム / RNA分子糊 / RNA結合リガンド / 光スイッチ / RNAスイッチ / RNA高次構造 |
Outline of Final Research Achievements |
We have developed an artificial RNA switch that can control the expression of a target protein by combining two of our key technologies, 1) synthetic RNA binding small molecular ligands that bind specifically to the target RNA and thereby induce the secondary and tertiary structure changes of the RNA (molecular glue for RNA), and 2) ribozyme whose structure and catalytic function is controlled by the molecular glue. We successfully created RNA switches that share the core operating system described above but exhibit different responses; OFF switch where gene expression levels are inhibited by the ligand, ON switch where expression levels are increased by the ligand, and ON/OFF reversibly switch where expression levels are controlled bidirectionally by light stimuli. These RNA switches are functional in human-cultured cell models.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、RNA結合小分子リガンドと外部刺激となる光を用いて、ヒト培養細胞内における標的タンパク質の発現を自在に制御可能な人工システムを構築した。標的遺伝子下流にRNAスイッチとなる配列を挿入することで動作するコンパクトな制御系であり、任意のタイミングで形質を発現するモデル細胞構築など合成生物学的意義が高い。本研究で採用し、実証したRNA結合小分子リガンドを基盤とする戦略は、RNA高次構造と機能を相関付けることのできる様々な機能性RNAに適用することができ、細胞機能の精密制御を通じた機能解明、創薬に資する分子作用機序の創出に貢献する。
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Report
(5 results)
Research Products
(34 results)